NM_173791.5:c.*5770T>A

Variant names:

• chr10-117277498-A-T
• rs10377
• NM_173791.5:c.*5770T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173791.5(PDZD8):​c.*5770T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDZD8 NM_173791.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.82
• Publications: 8 publications found

Genes affected

PDZD8 (HGNC:26974): (PDZ domain containing 8) Predicted to enable lipid binding activity and metal ion binding activity. Involved in several processes, including mitochondrial calcium ion homeostasis; mitochondrion-endoplasmic reticulum membrane tethering; and regulation of cell morphogenesis. Located in endoplasmic reticulum membrane and mitochondria-associated endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC18A2 (HGNC:10935): (solute carrier family 18 member A2) This gene encodes an transmembrane protein that functions as an ATP-dependent transporter of monoamines, such as dopamine, norepinephrine, serotonin, and histamine. This protein transports amine neurotransmitters into synaptic vesicles. Polymorphisms in this gene may be associated with schizophrenia, bipolar disorder, and other neurological/psychiatric ailments. [provided by RefSeq, Jun 2018]

SLC18A2 Gene-Disease associations (from GenCC):

• brain dopamine-serotonin vesicular transport disease

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P
• parkinsonism-dystonia, infantile, 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD8	NM_173791.5	c.*5770T>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000334464.7	NP_776152.1
SLC18A2	NM_003054.6	c.*232A>T		3_prime_UTR_variant	Exon 16 of 16	ENST00000644641.2	NP_003045.2
PDZD8	XM_005269518.5	c.*5770T>A		3_prime_UTR_variant	Exon 4 of 4		XP_005269575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZD8	ENST00000334464.7	c.*5770T>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_173791.5	ENSP00000334642.5
SLC18A2	ENST00000644641.2	c.*232A>T		3_prime_UTR_variant	Exon 16 of 16		NM_003054.6	ENSP00000496339.1
SLC18A2	ENST00000497497.1	n.2193A>T		non_coding_transcript_exon_variant	Exon 15 of 15	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 117294 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 59930

African (AFR) AF: 0.00 AC: 0 AN: 3750

American (AMR) AF: 0.00 AC: 0 AN: 3986

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4786

East Asian (EAS) AF: 0.00 AC: 0 AN: 10134

South Asian (SAS) AF: 0.00 AC: 0 AN: 2426

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6688

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 568

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 76854

Other (OTH) AF: 0.00 AC: 0 AN: 8102

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Benign	0.81
PhyloP100		2.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10377; hg19: chr10-119037009;